POS0477 RELATIONSHIP BETWEEN SHARED EPITOPE STATUS AND REFRACTORY RHEUMATOID ARTHRITIS
Authors: K. Wipfler, S. Pedro, U. Sbarigia, F. Zazzetti, A. Sheahan, I. Lin, E. Alemao, K. Michaud
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Despite major advances in rheumatoid arthritis (RA) treatment and the improved outcomes that have been associated with the expanding number of advanced therapies available, a substantial number of patients are refractory to multiple biologics. To understand the mechanisms behind refractory RA (reRA) and ultimately improve therapies tailored to individuals, a better understanding of associated factors is necessary. The shared epitope (SE) is an amino acid sequence motif coded by several HLA-DRB1 alleles that are overrepresented among people with RA and is associated with the production of anti-citrullinated protein antibodies. <h3>Objectives</h3> To characterize the relationship between SE status and risk of developing refractory RA. <h3>Methods</h3> Participants in FORWARD, The National Databank for Rheumatic Diseases, with RA, high-resolution HLA-DRB1 typing, no history of biologic use at study entry, and subsequent exposure to one or more biologics were included. The reRA group included participants with exposure to at least three biologics while under observation. Those who used a single biologic with continued use for at least two years during observation comprised the comparison non-refractory group. Descriptive statistics for each group were calculated at initiation of first biologic. Significance was assessed with Fisher's exact tests and Mann-Whitney U tests (p&lt;0.05), as appropriate. Logistic regression was used to determine the relationship between shared epitope status and baseline odds of becoming refractory. <h3>Results</h3> Characteristics of the 70 participants that met inclusion criteria are presented in Table 1. Several covariates varied significantly by refractory group, but these differences were attenuated in adjusted models. SE positive individuals had significantly lower odds of becoming refractory, a relationship that remained consistent with varying model complexity (Figure 1; OR [95% CI] 0.16 [0.05, 0.49] in univariate model; p=0.001). HLA-DRB1*04:01 was the only SE positive allele independently associated with nonrefractory status (p=0.036; data for other alleles not shown). <h3>Conclusion</h3> In this cohort, individuals with RA who are SE positive were less likely to be refractory to multiple biologics. This relationship appears to be primarily the result of the HLA-DRB1*04:01 allele rather than any other alleles associated with SE positivity. These findings suggest that SE positive individuals with RA are more likely to find success with their first biologic, while SE negative individuals may be more likely to cycle through multiple biologics. Ongoing and future work will investigate this relationship further and assess whether these results remain consistent when using varying definitions of reRA. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Kristin Wipfler: None declared, Sofia Pedro: None declared, Urbano Sbarigia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen, Federico Zazzetti Shareholder of: Johnson &amp; Johnson, Employee of: Janssen, Anna Sheahan Employee of: Janssen, Iris Lin Shareholder of: Johnson &amp; Johnson, Employee of: Janssen, Evo Alemao Shareholder of: Johnson &amp; Johnson, Employee of: Janssen, Kaleb Michaud: None declared.